Early Branching Research Articles

The phylogeny of Acetobacteraceae : photosynthetic traits and deranged respiratory enzymes

ABSTRACT We present here a comprehensive phylogenomic analysis of Acetobacteraceae , a vast group of alphaproteobacteria that has been widely studied for their economic importance. Our results indicate that the ancestor of Acetobacteraceae most likely was photosynthetic and evolved via a progressive transition from versatile photoferrotrophy to the incomplete oxidation of organic substrates defining acetous physiology. Vestigial signs of photosynthetic carotenoid metabolism are present in non-photosynthetic acetous taxa that have lost cytochrome oxidase, while their sister taxa retain such traits. The dominant terminal oxidase of acetous bacteria, the bo 3 ubiquinol oxidase, is derived from duplication and diversification of operons present in Acidocella taxa that have lost photosynthesis. We analyzed the bioenergetic traits that can compensate for the electron transfer function of photosynthetic reaction centers or constitute alternative pathways for the oxidoreduction of c -type cytochromes, such as iron oxidation. The latter pathway bypasses the deranged cytochrome bc 1 complex that is characteristically present in acidophilic taxa due to the loss of conserved ligands in both the Rieske iron-sulfur protein and cytochrome b subunit. The deranged or non-functional bc 1 complex may be retained for its structural role in stabilizing Complex I. The combination of our phylogenetic analysis with in-depth functional evaluations indicates that the order Acetobacterales needs to be emended to include three families: Acetobacteraceae sensu stricto , Roseomonadaceae fam. nov., and Acidocellaceae fam. nov. IMPORTANCE Acetobacteraceae are one of the best known and most extensively studied groups of bacteria, which nowadays encompasses a variety of taxa that are very different from the vinegar-producing species defining the family. Our paper presents the most detailed phylogeny of all current taxa classified as Acetobacteraceae , for which we propose a taxonomic revision. Several of such taxa inhabit some of the most extreme environments on the planet, from the deserts of Antarctica to the Sinai desert, as well as acidic niches in volcanic sites like the one we have been studying in Patagonia. Our work documents the progressive variation of the respiratory chain in early branching Acetobacteraceae into the different respiratory chains of acidophilic taxa such as Acidocella and acetous taxa such as Acetobacter . Remarkably, several genomes retain remnants of ancestral photosynthetic traits and functional bc 1 complexes. Thus, we propose that the common ancestor of Acetobacteraceae was photosynthetic.

Case Series on Double-Barrel Stenting for the Renal Arteries Associated With Fenestrated Repair (FEVAR) of Complex Anatomy Aortic Aneurysms.

The double-barrel stenting (DBS) is a technique in which 2 parallel stents are simultaneously deployed through the same reinforced fenestration, into 2 adjacent target vessels. Prior reports describe the application of this technique for the treatment of superior mesenteric artery dissection with aneurysmal degeneration, coronary artery bifurcations, aortic arch branches, and intracranial aneurysms. The DBS technique is particularly useful in the context of fenestrated repair (FEVAR) of complex anatomy aortic aneurysms when the origin of visceral arteries branch off the aorta very close to each other or present early branches. We herein describe a case series including 7 patients who underwent a FEVAR procedure for thoracoabdominal and juxtarenal aortic aneurysms in which the presence of accessory renal arteries (ARA) or early renal branches was the reason for the application of this technique. Technical success was 100% and all stents were patent in the last follow-up CT scan (follow-up range: 1.8-62.8 months). There was only 1 small endoleak from indetermined source potentially related to the DBS, but the aneurysm sac decreased in size during follow-up and no secondary intervention was needed. Therefore, the DBS technique is a viable option for the incorporation of ARA or early renal branches to a fenestrated repair of aortic aneurysms with complex anatomy.

Components of iron–Sulfur cluster assembly machineries are robust phylogenetic markers to trace the origin of mitochondria and plastids

Establishing the origin of mitochondria and plastids is key to understand 2 founding events in the origin and early evolution of eukaryotes. Recent advances in the exploration of microbial diversity and in phylogenomics approaches have indicated a deep origin of mitochondria and plastids during the diversification of Alphaproteobacteria and Cyanobacteria, respectively. Here, we strongly support these placements by analyzing the machineries for assembly of iron–sulfur ([Fe–S]) clusters, an essential function in eukaryotic cells that is carried out in mitochondria by the ISC machinery and in plastids by the SUF machinery. We assessed the taxonomic distribution of ISC and SUF in representatives of major eukaryotic supergroups and analyzed the phylogenetic relationships with their prokaryotic homologues. Concatenation datasets of core ISC proteins show an early branching of mitochondria within Alphaproteobacteria, right after the emergence of Magnetococcales. Similar analyses with the SUF machinery place primary plastids as sister to Gloeomargarita within Cyanobacteria. Our results add to the growing evidence of an early emergence of primary organelles and show that the analysis of essential machineries of endosymbiotic origin provide a robust signal to resolve ancient and fundamental steps in eukaryotic evolution.

Early Molecular Steps in Human Bone Marrow Stem Cell Differentiation Trajectories

Understanding the molecular signatures of human hematopoietic stem/progenitor cells (HSCPs) and gene network changes leading to differentiation induction are of utmost importance to achieve therapeutic hematopoietic stem cell (HSC) expansion. The identification of surface markers has improved the prospective isolation of human bone marrow HSCs over the last decades, but the isolated population still remains very heterogeneous. Single cell sequencing approaches have the potential to unbiased assort stem cells along their differentiation stages and trajectories, and to decipher molecular markers in differentiation hierarchies. However, whole transcriptome single cell sequencing often suffers from inadequate detection of low-expressed genes with increased drop-outs. To address this limitation and to provide sensitive mRNA quantification in human HSPCs, we developed a selected targeted gene panel (600 genes) in combination with 50 protein markers to cover most relevant genes/proteins of early HSPC differentiation and cell cycle status. We employed single cell CITE-Seq (cellular indexing of transcriptomes and epitopes by sequencing) based multi-omic profiling to >60.000 high-quality FACS-enriched human bone marrow HSPCs (CD34 + and CD34 +CD38 - cells) from 15 healthy donors representing young, mid and old age groups. Here, we demonstrate the most comprehensive molecular map of early human HSC differentiation and provide evidence of early branching points into lineage trajectories across different age groups using Slingshot pseudotime analysis. Our data demonstrate that the HSC branched into two main lineages, with the first branching point giving rise to megakaryocytic and erythroid progenitors (MKP/ERP), followed by lymphoid and myeloid progenitors (LMP/MDP). As expected, the most immature HSCs were defined by high expression of CD34, CD90, CRHBP, HOPX, HLF, MLLT3. However, we observed a number of hitherto undescribed HSC markers. The MKP/ERP lineage was defined by GATA1, TFRC, CD36, MPL and VWF expression. Furthermore, we found CD274, the Programmed Cell Death receptor ligand 1, to be selectively expressed in the MKP cluster. Re-clustering and trajectory analysis of the most immature CD34 +CD38 -/low cells confirmed early lineage commitment, suggesting that an MKP/ERP development does not include myeloid or lymphoid progenitors. A similar pattern was observed for all age groups. Interestingly, we observed increased expression of novel marker genes ( HLA-E, DLK1, ADGRG6, ADGRG1, MMRN1) and proteins (CD137 and CD273) in the most immature HSCs. Besides a gradual upregulation of CD38 along differentiation, differentiated cells showed lower CD45 levels. Furthermore, MKP/ERP committed cells showed a downregulation of SPINK2. TradeSeq analysis defined the continuous single cell expression changes in genes and markers upon early differentiation and lineage commitment, allowing the detection of decision-making gene networks. Our data adds further evidence to the revised model of hematopoiesis that challenges the dogma of a common myeloid progenitor giving rise to erythroid, megakaryocytic and myeloid cells. Furthermore, we see a structured hierarchical organization with a sequential loss of lineage potential and not an early commitment of uni-lineage restricted precursors. We report on the upregulation of ADGRG6, ADGRG1, DLK1, HLA-E, MMRN1 CD137 and CD273 in the most immature HSCs. Molecular and functional characterization of CD273 hi and low HSCs are presented in an adjacent report by our group at this meeting (Schmachtel et al.). In conclusion, we provide a valuable resource for the continuous regulation of genes and surface proteins along early differentiation of very immature human HSCs.

Comparative and phylogenetic analyses of mitochondrial genomes in Elateridae (Coleoptera: Elateroidea).

The click-beetles (Elateridae) are a species-rich beetle family that is easily recognizable. They are distributed in all zoogeographical regions with over 11,000 species. Comparative studies of the structural characteristics of mitochondrial genomes (mitogenomes), as well as phylogenetic relationships of click-beetles, can improve our understanding of mitogenomic evolution. In this study, we determined four mitogenomes from Elateridae by next-generation sequencing. The four mitogenomes were 16,005 to 16,930 bp in length with 37 typical genes and a control region (A + T-rich region). Combined with previously reported elaterid mitogenomes, all PCGs initiate with either the standard start codon of ATN or TTG. According to the nonsynonymous/synonymous mutation ratio (Ka/Ks) of all PCGs, the highest and the lowest evolutionary rates were found for atp8 and cox1, respectively. Among the control regions of the four mitogenomes, several different patterns and numbers of tandem repeats were identified, which was the primary cause of the length variation in control regions. Phylogenetic analyses were conducted based on 13 protein-coding genes and two ribosomal RNA genes from 33 species of Elateridae and two outgroups. The Bayesian inference and maximum likelihood trees had an identical topological structure. The monophyly of Cardiophorinae, Agrypninae and Elaterinae was recovered with high support in all topologies, and the Tetralobinae was placed as the earliest branch in the Elateridae. Expanding the availability of mitogenomic and genomic data from a broader range of click-beetles could provide more clarity on the disputed relationships among subfamilies within Elateridae.

Variability and evolution of gene order rearrangement in mitochondrial genomes of arthropods (except Hexapoda)

In the species-rich Phylum Arthropoda, the mitochondrial genome is relatively well conserved both in terms of number and order of genes. However, specific clades have a ‘typical’ gene order that differs from the putative arthropod ancestral arrangement. The aim of this work was to compare the rate of mitochondrial gene rearrangements at inter- and intra-taxonomic levels in the Arthropoda and to postulate the most parsimonious ancestral orders representing the four major arthropod lineages. For this purpose, we performed a comparative genomic analysis of arthropod mitochondrial genomes available in the NCBI database. Using a combination of bioinformatics methods that examined mitochondrial gene rearrangements in 464 species of arthropods from three subphyla (Chelicerata, Myriapoda, and Crustacea [except Hexapoda, previously analyzed]), we observed differences in the rate of rearrangement within major lineages. A higher rate of mitochondrial genome rearrangement was observed in Crustacea and Chelicerata compared to Myriapoda. Likewise, early branching clades exhibit less variability in mitochondrial genome order than late branching clades, within each subphylum. We identified ‘hot regions’ in the mitochondrial genome of each studied subphylum, and postulated the most likely ancestral gene order in each subphylum and taxonomic order. Our work provides new evidence on the evolutionary dynamics of mitochondrial genome gene order in arthropods and new mitochondrial genome architectures in different taxonomic divisions within each major lineage of arthropods.

VARIATIONS IN THE ORIGIN OF PROFUNDA BRACHII ARTERY FROM BRACHIAL ARERTY-SYSTEMATIC REVIEW

Objective: The profunda brachii artery (PBA) is a chief artery in anterior compartment of the arm for the nutritional source. Knowledge of variations in the origin and branching is helpful for the surgeon during catheterization and harvesting of lateral flaps. Methods: During the routine dissection for medical undergraduate students we found variations in the branching pattern of PBA in 72 arms from 36 cadavers in the Department of Anatomy, Viswabharathi Medical College, Penchikalapadu, and Kurnool, over 5 years. We preserved all the variations carefully. Results: We observed PBA in all the cadavers, patterns of origin, branches, and termination were recorded. In 96.9% of cadavers artery arises from the brachial artery (BA), in 1.4% from the axillary artery, and in 1.7% cadavers from a common stem with the superior ulnar collateral arteries. In 11.1% and 16.7% of the cadavers showed duplication and early branching. Conclusion: Humeral fractures and BA catheterization the incidence of duplication and early branching make it vulnerable to inadvertent injury and may complicate lateral arm flaps. Pre-operative angiographic evaluation is therefore recommended.

Renal vascular disparities among kidney donors presented at renal transplant unit- A single centre study

Renal vasculature has been reported to show anatomical variations, which may lead to surgical complications. The pattern of renal vascular variations in Pakistani population is not well reported. Thus, this study was designed to assess the renal vascularity among kidney donors and correlate with age, gender and site of vessels. A total of 223 healthy volunteers underwent evaluation for kidney donation at the Radiology Department, DOW University Hospital, Karachi, Pakistan from January 2020 to July 2022 were included. The assessment of renal vasculature was done on computed (CT) angiogram. Renal vascular variations were found in 112 (50.2%), 59.8% were seen in males and 40.2% in females. On right side 50% vascular anomalies were found followed by left side with 27% and 22% on both sides. The arterial variants included accessory renal artery seen in 76 (67.8%) individuals, out of which 13.2% had in upper polar, 26.3% in hilum, 36.8% in lower polar, while 23.7% of early branching was observed. Ten retro-aortic, fourteen accessory renal veins and six bifurcation renal veins, along with six early branching renal veins, were present. Patient who received donor nephrectomy, the outcomes of the operation were completely consistent with the results of the CTA. According to this study, Pakistani population have differences in their renal venous and arterial anatomy, which can significantly influence surgical procedures.

Pulmonary Vein Remodeling Between Atrial Fibrillation Subtypes: A Matched Comparison Cardiac Computed Tomography-Based Study Between Patients With Paroxysmal and Persistent Atrial Fibrillation

Although pulmonary vein (PV) isolation is the cornerstone for atrial fibrillation (AF) ablation; no data exist comparing the PV anatomy between the AF subtypes directly. We aimed to compare the PV anatomic characteristics between paroxysmal AF (PAF) and persistent AF (PeAF) in a matched population using cardiac computed tomography. A total of 58 patients with PeAF (with cardiac computed tomography before the first AF ablation procedure, absence of valvular disease/previous cardiac intervention), and 58 age-, gender-, and body surface area-matched patients with PAF were evaluated for left atrial (LA) and PV anatomy: ostial area, ovality index, and transverse/frontal angles. In the PeAF versus PAF group, other than a higher LA volume index; the PV ostial areas were significantly larger (between 64 and 101mm2, p <0.001 for all PVs; remaining valid after LA volume index adjustment for left superior PV [LSPV], left inferior PV [LIPV], and right superior PV); the left PVs were less oval (0.7 to 0.11 ovality index decrease, p=0.039 for LSPV; p=0.012 for LIPV); and the LSPV (p=0.019), LIPV (p <0.001), and right inferior PV (p=0.029) were more posteriorly directed; whereas the LSPV (p=0.002) and right superior PV (p=0.043) were more superiorly directed. The incidence of anatomic variations or early branching was not different. This study showed significant anatomic PV differences between patients with PeAF and PAF in terms of PV orientation, ostial size, and ovality. Anticipating such anatomic differences may aid in choosing the adequate catheter design and technology for PeAF ablation.

The evolution of endoparasitism and complex life cycles in parasitic platyhelminths

Within flatworms, the vast majority of parasitism is innate to Neodermata, the most derived and diversified group of the phylum Platyhelminthes.1,2 The four major lineages of Neodermata maintain various combinations of life strategies.3 They include both externally (ecto-) and internally feeding (endo-) parasites. Some lineages complete their life cycles directly by infecting a single host, whereas others succeed only through serial infections of multiple hosts of various vertebrate and invertebrate groups. Food sources and modes of digestion add further combinatorial layers to the often incompletely understood mosaic of neodermatan life histories. Their evolutionary trajectories have remained molecularly unresolved because of conflicting evolutionary inferences and a lack of genomic data.4 Here, we generated transcriptomes for nine early branching neodermatan representatives and performed detailed phylogenomic analyses to address these critical gaps. Polyopisthocotylea, mostly hematophagous ectoparasites, form a group with the mostly hematophagous but endoparasitic trematodes (Trematoda), rather than sharing a common ancestor with Monopisthocotylea, ectoparasitic epithelial feeders. Phylogenetic placement of the highly specialized endoparasitic Cestoda alters depending on the model. Regardless of this uncertainty, this study brings an unconventional perspective on the evolution of platyhelminth parasitism, rejecting a common origin for the endoparasitic lifestyle intrinsic to cestodes and trematodes. Instead, our data indicate that complex life cycles and invasion of vertebrates' gut lumen, the hallmark features of these parasites, evolved independently within Neodermata. We propose the demise of the traditionally recognized class Monogenea and the promotion of its two subclasses to the class level as Monopisthocotyla new class and Polyopisthocotyla new class.

Morphological and histological investigation of the conduction system in the equine atrial muscle sleeve of pulmonary veins.

Atrial fibrillation is the most common arrhythmia in horses causing poor performance. The role of pulmonary vein triggers in the pathogenesis has been identified in horses. Ablation methods have been investigated, but the available information on anatomical, histological and immunohistochemical assessment of the pulmonary vein ostia and the conduction system of the myocardial sleeve is still limited. The aim of the study was to describe the morphological properties of the myocardial sleeve in healthy horses. Cross-sectional. Eighty-three equine hearts were dissected. The number and diameters of pulmonary vein ostia were determined, and anatomical localisation was described. Fifty-eight tissue samples were collected for routine histology and 12 of these were used for immunohistochemistry (connexin 43, 45, S100, and tyrosine hydroxylase antibodies). The mean number of pulmonary vein ostia was 4.5 (4 veins: 46 horse, 5 veins: 31 horses, 6 veins: 6 horses). Diameters (mean ± SD) of the main ostia were as follows: vein I: 20.2 ± 7.0 mm, vein II: 32.7 ± 7.1 mm, vein III: 33.4 ± 5.9 mm, vein IV: 18.1 ± 4.5 mm. Diameters of supernumerary vein ostia varied between 3.0 and 28.0 mm (11.5 ± 5.5 mm). Early branching was found in 26 horses (31.3%) and 30 veins (vein I: 14, vein II: 9, vein III: 5, vein IV: 2). Histology confirmed the presence of a muscle sleeve composed of myocardial tissue in each pulmonary vein. S100 and TH positivity was detected in each vein, and it confirmed the presence of adrenergic and non-adrenergic nerve fibres within the myocardial sleeve. Cx43 and 45 positivity were also found in each vein indicating the presence of gap junctions. The effect of bodyweight on pulmonary vein dimensions is unknown. Future ablation techniques should consider that conductive tissue is present in the entire myocardial sleeve in all pulmonary vein ostia.

A large sample of newly identified carbon-deficient red giants from APOGEE

ABSTRACT Based on the Apache Point Observatory Galactic Evolution Experiment survey we conducted a search for carbon-deficient red giants (CDGs). We found 103 new CDGs, increasing the number in the literature by more than a factor of 3. CDGs are very rare, representing 0.03 per cent of giants. They appear as an extended tail off the normal carbon distribution. We show that they are found in all components of the Galaxy, contrary to previous findings. The location of CDGs in the Hertzsprung–Russell diagram (HRD) shows that they are primarily intermediate-mass stars ($2-4~\rm {M}_{\odot }$). Their extended distribution may indicate that CDGs can also sometimes have $M \lt 2.0~\rm {M}_{\odot }$. We attempted to identify the evolutionary phases of the CDGs using stellar model tracks. We found that the bulk of the CDGs are likely in the subgiant branch or red clump phase, whereas other CDGs may be in the red giant branch or early asymptotic giant branch phases. Degeneracy in the HRD makes exact identification difficult. We examined their C, N, and O compositions and confirmed previous studies showing that the envelope material has undergone extensive hydrogen burning through the CN(O) cycle. The new-CDGs have [C+N+O/Fe] that generally sum to zero, indicating that they started with scaled-solar composition. However, the previously known-CDGs generally have [C+N+O/Fe] &amp;gt; 0.0, indicating that some He-burning products were added to their envelopes. As to the site(s) in which this originally occurred, we do not find a convincing solution.

Early divergence and gene exchange highways in the evolutionary history of Mesoaciditogales.

The placement of a non-hyperthermophilic order Mesoaciditogales as the earliest branching clade within the Thermotogota phylum challenges the prevailing hypothesis that the last common ancestor of Thermotogota was a hyperthermophile. Yet, given the long branch leading to the only two Mesoaciditogales described to-date, the phylogenetic position of the order may be due to the long branch attraction artifact. By testing various models and applying data recoding in phylogenetic reconstructions, we observed that early branching of Mesoaciditogales within Thermotogota is strongly supported by the conserved marker genes assumed to be vertically inherited. However, based on the taxonomic content of 1,181 gene families and a phylogenetic analysis of 721 gene family trees, we also found that a substantial number of Mesoaciditogales genes are more closely related to species from the order Petrotogales. These genes contribute to coenzyme transport and metabolism, fatty acid biosynthesis, genes known to respond to heat and cold stressors, and include many genes of unknown functions. The Petrotogales comprise moderately thermophilic and mesophilic species with similar temperature tolerances to that of Mesoaciditogales. Our findings hint at extensive horizontal gene transfer between, or parallel independent gene gains by, the two ecologically similar lineages, and suggest that the exchanged genes may be important for adaptation to comparable temperature niches.

Distal stenting technique for coil embolization of early branch aneurysms of middle cerebral artery

Background and purposeStent-assisted coil embolization of early branch aneurysms of the middle cerebral artery (MCA) can sometimes be challenging due to the small diameter and acute angle of the branches. This study aimed to analyze the treatment results and report the feasibility and outcomes of the distal stenting technique for these aneurysms. Materials and methodsThe distal stenting technique was used for 15 wide-neck MCA aneurysms (females, 10; males, 5; mean age, 65.1 years) originating from the early branch between December 2018 and October 2021. The average sizes of the dome, depth, and neck of the aneurysms were 4.17 mm (range: 2.99–6.21 mm), 2.86 mm (range: 1.82–3.72 mm), and 3.42 mm (range: 2.44–4.32 mm), respectively. ResultsThe average diameter of the stents was 4.0 mm (3.0 mm, 3; 4.0 mm, 6; 4.5 mm, 6). Stents were successfully deployed in all 15 aneurysms (100%). The average length of the procedure was 69 min (range: 45–117 min). On postoperative angiography, nine (60.0%) aneurysms were completely occluded, four (26.7%) had neck remnants, and two (13.3%) had contrast flow in the sac. During the procedure, vasospasm and thrombus formation occurred in one case each, but no neurological sequelae were observed. On follow-up digital subtraction angiography of the 10 aneurysms after an average of 13.7 months (range: 12–18 months), the branches were well preserved, and neck remnants were noted in four aneurysms (40.0%). No thromboembolic events occurred during the clinical follow-up. ConclusionThe distal stenting technique using an open-cell stent can be a good option for coil embolization of early branch MCA aneurysms.

The formation of proto-austronesians: insights from a revised phylogeography of the paternal founder lineage.

Previous studies suggested that the Y-chromosome haplogroups O2-N6-B451-AM01756 and O1a-M119 are two founder lineages of proto-Austronesians at about five thousand years ago. The objective of this study was to investigate the formation of proto-Austronesians from the perspective of the paternal gene pool. In this study, we developed a highly evised phylogenetic tree with age estimates for haplogroup O2-N6 and early branches of O1a-M119 (M110, F1036, and F819). In addition, we also explored the geographical distribution of eight sub-branches of O2-N6 and O1a-M119, and spatial autocorrelation analysis was conducted for each sub-branch. The paternal lineage combination of proto-Austronesians is a small subset of a diverse gene pool of populations from the mainland of East Asia. The distribution map and results of the spatial autocorrelation analysis suggested that the eastern coastal region of northern China is likely the source of lineage O2-N6 while the coastal region of southeastern China is likely the diffusion center of early branches of O1a-M119. We developed an evolutionary diagram for Austronesians and their ancestors in the past 18,000years. We proposed that the millet farming community in North China is the common ancestor group of the Austronesians and the Han people, while the diverse ancient people in the southeast coastal areas of East Asia form the common ancestor group of the Austronesians and the East Asian mainland population. The demographic history of multiple ancestral groups of the most recent common ancestor group itself in the more ancient period is helpful to understand the deep roots of the genetic components and cultural traditions of Austronesians.

Early left bundle branch pacing in heart failure with mildly reduced ejection fraction and left bundle branch block

Left bundle branch pacing (LBBP) achieves resynchrony and improves cardiac function in heart failure (HF) patients with reduced ejection fraction (EF) by correcting left bundle branch block (LBBB). Few data on the efficacy of early LBBP in HF with mildly reduced EF (HFmrEF) and LBBB have been reported. The purpose of this study was to explore the efficacy of early LBBP in patients with HFmrEF and LBBB. Consecutive patients with HFmrEF (left ventricular EF [LVEF] 35%-50%) and LBBB were prospectively enrolled to receive LBBP (Early-LBBP group) plus guideline-directed medical therapy (GDMT) or GDMT alone (GDMT group). Study outcomes included changes in LVEF, LV end-diastolic diameter (LVEDD), New York Heart Association (NYHA) functional classification, and N-terminal pro-brain natriuretic peptide (NT-proBNP), and clinical events (HF rehospitalization or syncope). Subgroup analysis compared efficacy of LBBP between patients with LBBB only without comorbidities or late gadolinium enhancement (LGE) (LBBB-Only group) and patients with either comorbidities or LGE (LBBB-Combined group). Fifty-four patients were enrolled and analyzed (37 Early-LBBP group; 15 GDMT group). LBBP achieved greater improvement in LVEF (+14.75% ± 7.37% vs -2.42% ± 2.84%; P <.001), reduction of LVEDD (-7.51 ± 5.40 mm vs -0.87 ± 4.36 mm; P <.001) and NYHA classification (-0.84 ± 0.76 vs -0.13 ± 0.74; P = .004), and similar reduction of NT-proBNP (-408.83 ± 920.29 pg/mL vs -229.05 ± 1579.17 pg/mL; P = .610) at 6 months. Early LBBP showed significantly reduced clinical events (0.0% vs 40.0%; P <.001) after 20.68 ± 13.55 months of follow-up. Subgroup analysis showed patients in the LBBB-Only group benefited more from LBBP with regard to LVEF improvement and LVEDD reduction than the LBBB-Combined group. Early LBBP with GDMT demonstrated greater improvement of cardiac function and reduced clinical events than GDMT alone in patients with HFmrEF and LBBB.

A complete species-level phylogeny of the Erythrura parrotfinches (Aves: Estrildidae)

Identifying species boundaries and phylogenetic relationships among groups of closely related species provides a necessary framework for understanding how biodiversity evolves in natural systems. Here we present a complete phylogeny of the avian genus Erythrura (family Estrildidae) commonly known as parrotfinches, which includes species threatened by habitat loss and the pet trade. Using both mitogenome and reduced-representation genome-wide nuclear DNA sequence data, we reconstructed the evolutionary history of the group by sampling all 12 recognized species, four of which had not previously been studied in a phylogenetic context. We included intra-species geographic sampling that allowed us to comment on species limits in some taxa. We recovered the Gouldian Finch (Chloebia gouldiae) of Australia which has often been placed in the monotypic genus Chloebia, as being sister to a clade comprising all Erythrura species. In addition, we recovered a well-supported clade comprising eight species distributed throughout the Pacific Island eco-region, whereas those species occurring in continental southeast Asia, the Greater Sundas, and the Philippines, were recovered as earlier branching lineages. Of note was the early branching of the Fiji-endemic E. kleinschmidti which corroborates its unique phenotype. We also found a deep phylogenetic split (8.59% corrected, 7.89% uncorrected divergence in the mitochondrial gene ND2) between the Java and Philippine populations of E. hyperythra, indicating unrecognized species-level diversity within this taxon. In contrast, genome-wide nuclear data suggested that the New Guinea endemic species E. papuana is embedded within the widespread species E. trichroa in all phylogenetic reconstructions, corroborating previously published mitochondrial data that suggested a similar pattern. By generating a phylogenetic hypothesis for the relationships among all species of Erythrura parrotfinches, we provide a framework for better understanding the extant diversity and evolutionary history of this group.

The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer.

The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.

Regeneration in calcareous sponge relies on 'purse-string' mechanism and the rearrangements of actin cytoskeleton.

The crucial step in any regeneration process is epithelization, i.e. the restoration of anepithelium structural and functional integrity. Epithelization requires cytoskeletal rearrangements, primarily of actin filaments and microtubules. Sponges (phylum Porifera) are early branching metazoans with pronounced regenerative abilities. Calcareous sponges have a unique step during regeneration: theformation of a temporary structure, calledregenerative membrane which initially covers a wound. It forms due to the morphallactic rearrangements of exopinaco- and choanoderm epithelial-like layers. The current study quantitatively evaluates morphological changes and characterises underlying actin cytoskeleton rearrangements during regenerative membrane formation in asconoid calcareous sponge Leucosolenia variabilis through a combination of time-lapse imaging, immunocytochemistry, and confocal laser scanning microscopy. Regenerative membrane formation has non-linear stochastic dynamics with numerous fluctuations. The pinacocytes at the leading edge of regenerative membrane form a contractile actomyosin cable. Regenerative membrane formation either depends on its contraction or being coordinated through it. The cell morphology changes significantly during regenerative membrane formation. Exopinacocytes flatten, their area increases, while circularity decreases. Choanocytes transdifferentiate into endopinacocytes, losing microvillar collar and flagellum. Their area increases and circularity decreases. Subsequent redifferentiation of endopinacocytes into choanocytes is accompanied by inverse changes in cell morphology. All transformations rely on actin filament rearrangements similar to those characteristic of bilaterian animals. Altogether, we provide here a qualitative and quantitative description of cell transformations during reparative epithelial morphogenesis in a calcareous sponge.

2D approach to reconstruct the evolutionary history of clevelandellids (Ciliophora, Armophorea) inhabiting the hindgut of the Panesthiinae cockroaches

AbstractThe ciliate order Clevelandellida unites endosymbionts of the digestive tract of a variety of invertebrates and vertebrates. In the present study, the primary and secondary structures of nuclear and hydrogenosomal rRNA molecules were employed to reconstruct the phylogenetic relationships and to estimate the divergence times of clevelandellids inhabiting the hindgut of the Panesthiinae cockroaches. The secondary structure information was incorporated in phylogenetic analyses using two different strategies, viz., indirectly through 2D‐guided alignments and directly through so‐called pseudo‐protein data. Nuclear and hydrogenosomal markers carried a consistent phylogenetic signal and robustly supported the monophyletic origin of the family Clevelandellidae as well as of its four genera. According to Bayesian relaxed molecular clock analyses, the last common ancestor (LCA) of the family Clevelandellidae very likely emerged during the Late Cretaceous in the Oriental region. Its descendants most likely expanded to Australia in concert with the Neogene colonization and radiation of their host Panesthiinae cockroaches. Taking into account the time‐calibrated phylogenies and the fact that early branching members of the order Clevelandellida inhabit the digestive tracts of amphibians, it is tempting to speculate that the LCA of the Clevelandellida evolved in ectothermic vertebrates. Amphibians could have brought clevelandellids to the land, where they may have been transmitted to the cockroach digestive tract upon feeding on amphibian faeces.